Introduction to Organic and

Biochemistry
(CHE 124)
Reading Assignment
General, Organic, and Biological Chemistry: An Integrated Approach
3rd. Ed. Ramond
Chapter 12
Peptides, Proteins, and Enzymes
 Protein

• Linear, unbranched polymer of 50 or more

amino acids. Amino acids are connected
through peptide bonds (amide linkage).
• The linear sequence of amino acids folds into
a three dimensional structure.
 Functions of Proteins
• Enzymatic catalysis most chemical reactions in the cell are
carried out by enzymes ,which are globular proteins. They
increase the rate of chemical reactions by reducing the
energy of activation.

• Transport and storage small molecules are moved throughout

the cell by specific transporters. ie hemoglobin transports O2
in the blood.

• Mechanical support the high tensile strength of bone and skin

is due to the presence of collagen, a fibrous protein.

• Coordinate motion muscles are made mostly of proteins.

Contraction of muscles relies on the sliding motion of two
types of proteins, actin and myosin. Motion of a flagella and
movement of chromosomes in mitosis also relies on proteins.
 Functions of Proteins
• Generate and transmission of nerve impulses sending and
receiving messages between nerve cells requires receptor
proteins that detects the presence of acetylcholine.

• Control of growth and differentiation proteins turn the

expression of other proteins on and off by binding to specific
sequences on DNA.

• Immune protection antibodies are highly specific proteins that

identify and remove foreign substances from the cell.
 Definitions
• Glucogenic Amino Acids
– Carbon skeleton is converted into intermediate(s) that
can be used to synthesize glucose.
• Ketogenic Amino Acids
– Carbon skeleton is converted into intermediate(s) (acetyl
CoA or Acetoacetyl CoA) that can form ketone bodies or
fatty acids
– NOT substrate for glyconeogenesis
• Nonessential Amino Acids
– enzymes present for de novo synthesis of these amino
acids
• Essential Amino Acids – (TV FILM HWK)
– Organism lacks enzymes to synthesize the amino acids.
 Amino Acid Backbone

• 20 naturally occurring
amino acids are
incorporated into
proteins.
• Living systems contain
– L amino acids
 Amino Acids
• GLUCOGENIC BOTH KETOGENIC
NONESSENTIAL NONESSENTIAL NONESSENTAIL
– Alanine (A, Ala) – Tyrosine (Y, Tyr)
– Arginine (R, Arg)*
– Asparagine (N,Asn )
– Aspartate (D, Asp)
– Cysteine (C, Cys)
– Glutamate (E, Glu)
– Glutamine (Q, Gln)
– Glycine (G, Gly)
– Proline (P, Pro)
– Serine (S, Ser)

ESSENTIAL ESSENTIAL ESSENTAIL

(Val and His Three Methods) (Iley Trpped BOTH Phesants) KETONES in Leu of
Lysine
– Histidine (H, His)*
– Isoleucine (I, ile) --Leucine (L, Leu)
– Methionine (M, Met)
– Phenylalanine (F, Phe) -- Lysine (K, Lys)
– Threonin (T, Thr)
– Tryptophane (W, Trp)
– Valine (V, Val)

Essential: TV FILM HWK Updated 2014

 Cyclic (1)
Name Structure M.W. One Three Type R group
pKa

Proline 75 P Pro Nonpolar ----

• Proline is associated with bends, kinks or tight turns in protein

structure.
• Often followed by glycine in hairpin turns.
 Aliphatic (5)
Name Structure MW One Three Type R
group
pKa

Glycine 75 G Gly Nonpolar ----

Methyl

Alanine 89 A Ala Nonpolar ----

Valine 117 V Val Nonpolar ----

 Aliphatic (Cont’)
Name Structure MW One Three Type R
group
pKa

----
Leucine 131 L Leu Nonpolar

----
Isoleucine 131 I Ile Nonpolar

• Aliphatic-Nonaromatic hydrocarbon (H and C only).

– Nonpolar, hydrophobic
• Participate in hydrophobic interactions.
• Usually found inside proteins, away from the aqueous solvent,
 Sulfur Containing (2)
Name Structure MW One Three Type R
group
pKa

Sulfhydryl
Cysteine 121 C Cys Nonpolar 8.3

Methionine 149 M Met Nonpolar ----

• Cysteine may form disulfide bridges, which stabilize 3’

structure.
• Methionine is first amino acid incorporated in growing
peptide during translation.
 Aromatic (3)
Name Structure MW One Three Type R
group
pKa

Phenylalanine Phenyl
165 F Phe Nonpolar ----

Tryptophane 204 W Trp Nonpolar ----

Indole
 Aromatic (cont’) (Tyr is also hydroxyl containing)
Name Structure MW One Three Type R group
pKa

Tyrosine 181 Y Tyr Polar 10.9

Aromatic
• May participate in hydrophobic bonding
• May bind planar ligands via van der Waals stacking
• Absorb Ultraviolet light (approx. 280 n.m.)
• Tyrosine may hydrogen bond or donate a proton in catalysis
 Hydroxyl Containing (3)
Name Structure MW One Three Type R group
pKa

Serine Hydroxyl 105 S Ser Polar ----

Threonine 119 T Thr Polar ----

• Alcohols or hydroxyl-containing side chains

• Proton donors.
• Ser is at active site of some enzymes.
• Attachment of O-linked carbohydrates to proteins
 Acidic (2)
Name Structure MW One Three Type R
group
pKa

Aspartic Acid 133 D Asp Polar 3.9

(Aspartate) Carboxylic acid (Acidic)

Glutamic Acid Carboxylic acid 147 E Glu Polar 4.3

(Glutamate) (Acidic)

• Polar – charged (acidic), hydrophilic.

• Found at the Surface of proteins
• Often at active site of enzymes to donate / accept a proton.
 Neutral Amide (2)
Name Structure MW One Three Type R group
pKa

Asparagine Amido
132 N Asn Polar ----

Glutamine Amido
146 Q Gln Polar ----

• Polar – uncharged.
• Participates in hydrogen bonding.
 Basic (3)
Name Structure MW One Three Type R group
pKa

Amino
Lysine 146 K Lys Polar 10.8
(Basic)

Guanidinium
Arginine 174 R Arg Polar 12.5
(Basic)

Imidazole

Histidine 155 H His Polar 6.0

(Basic)

● Polar – charged (basic), hydrophilic.

● Located on the surface. May be involved in catalysis or metal binding.
 Amino acids may exist as
stereoisomers
The amino acid alpha carbon is chiral (except G)
• S (sinister) = left = counterclockwise
• R (rectus) = right = clockwise
– Most L amino acids have an S absolute configuration
The charge of an amino acid changes
with pH
 Amino acid residues are connected by
peptide bonds
• Peptide bond
– linear and planar
– not free to rotate
• Resonance
– partial double bond characteristics (Can you draw a resonance
structure?)

• Trans
– Hydrogen of the substituted amino group is trans to the
oxygen of the carbonyl group
• exception X-pro
 The peptide bond exhibit resonance
and, therefore, possesses double bond
character
• Peptide bond is planar with a bond length of 1.32 Å.
– Intermediate between C-N (1.49 Å) and C=N (1.27 Å)
• Peptide bond is uncharged.
Protein has amino (N) terminal and
carboxyl (C) terminal end
 Four Levels of Protein Structure
• Primary Structure
– linear sequence of amino acids.
• N-met-ala-pro-gly-asp-ala-his -C
• Secondary Structure
α (alpha) helix
β (beta) sheets
β (beta) turns
Ω (omega) loop
– hydrogen bonding between the carboxyl oxygen
and nitrogen hydrogen of the peptide chain
(back bone)
• Tertiary Structure
– folding of polypeptide chain as a result of
interactions between R-groups
– A domain is a unit of tertiary structure
• helix turn helix.
• helix loop helix
• zinc fingers
• leucine zipper
• Quaternary Structure
– interaction of different polypeptide chains
(subunits) to form a functional protein.
Alpha Helix: type of secondary structure
Proposed by Linus Pauling and Robert Corey (1951)

• Orientation is right handed helix

• Right hand = clockwise
• Left hand = counterclockwise
• Stabilized by hydrogen bonding between
– carbonyl oxygen
– NH group of peptide
• every fourth amino acid
• 3.6 amino acids per turn of helix
– Translation of 1.5 Å and rotation of 100
degrees.
• R- groups extend outward
• Helix is disrupted by
• proline
• large number of charged amino acids
– (e.g. Q, E, H, K, R)
• amino acids with bulky side chains
– (e.g.W)
• amino acids with branched R groups
– (e.g. V,I)
Helix turn Helix: A type of Domain
 Beta Pleated Sheet: type of secondary
structure
Proposed by Pauling and Corey (1951)

• Orientation of proteins is flat or pleated,

linear “sheet” of proteins.
• Stabilized by hydrogen bonding between
– Carbonyl oxygen
– NH group of peptide
• Adjacent amino acids are separated by
3.5 Å
• Strands may organize themselves into
several orientations
– Antiparallel
– Parallel
– Mixed (both antiparrellel and parallel)
• Beta bends
– contain proline and glycine
 Tertiary Structure
• Tertiary Structure
– folding of polypeptide chain as a result of interactions
between R-groups
 Quaternary Structure
• Quaternary Structure
– interaction of different polypeptide chains (subunits) to
form a functional protein.
– Myoglobin will be discussed later along with hemoglobin
– Hemoglobin is a α2β2 tetramer
 Denaturing Protein
• unfolding and disorganization of a
proteins secondary and tertiary
structure.
– Does not involve hydrolysis of peptide
bonds
– denaturing agents
• heat
• organic solvents
• Urea
• guanidinium chloride
• detergents
– SDS
• change in pH
– strong acids or bases
• Heavy metals
– Pb or Hg
– Reducing agents
• Beta mercaptoethanol – reduces
disulfide bonds